{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:04:29Z","timestamp":1790859869259,"version":"4.1.0"},"reference-count":69,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee on Scientific and Technological Cooperation of the Organization of Islamic Conference, Islamabad, Pakistan and International Foundation for Science","award":["I-1-F-6453-1"],"award-info":[{"award-number":["I-1-F-6453-1"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Berberis lycium<\/jats:italic>\n                      is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer\u2019s effect of berberine isolated from\n                      <jats:italic>Berberis lycium<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Root extract of\n                      <jats:italic>B<\/jats:italic>\n                      .\n                      <jats:italic>lycium<\/jats:italic>\n                      was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer\u2019s disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and \u03b2-secretase.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis.\n                      <jats:italic>In vivo<\/jats:italic>\n                      EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer\u2019s disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p&lt;0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of \u03b2-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with \u03b2-secretase in docking studies. Binding energies for interaction of \u03b2-secretase with berberine and drug Rivastigmine is -7.0 kcal\/mol and -5.8 kcal\/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer\u2019s disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing \u03b2-secretase expression in the Alzheimer\u2019s disease model.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0286349","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:44:40Z","timestamp":1698846280000},"page":"e0286349","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["RETRACTED: Bioassays guided isolation of berberine from Berberis lycium and its neuroprotective role in aluminium chloride induced rat model of Alzheimer\u2019s disease combined with insilico molecular docking"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8008-4595","authenticated-orcid":true,"given":"Hammad","family":"Ismail","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dania","family":"Khalid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durdana","family":"Waseem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8398-5364","authenticated-orcid":true,"given":"Muhammad Umar","family":"Ijaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erum","family":"Dilshad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan-ul","family":"Haq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Zeeshan","family":"Bhatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Anwaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madiha","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samreen","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"issue":"8","key":"pone.0286349.ref001","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1001\/archneur.60.8.1119","article-title":"Alzheimer disease in the US population: prevalence estimates using the 2000 census","volume":"60","author":"LE Hebert","year":"2003","journal-title":"Archives of Neurology"},{"issue":"7","key":"pone.0286349.ref002","first-page":"1450","article-title":"World health organization\u2019s global action plan on the public health response to dementia 2017\u20132025","volume":"13","author":"T Dua","year":"2017","journal-title":"Alzheimer\u2019s & Dementia: The Journal of the Alzheimer\u2019s Association"},{"key":"pone.0286349.ref003","first-page":"135","article-title":"Economic research on Alzheimer disease: a review of the literature","volume":"11","author":"RL Ernst","year":"1997","journal-title":"Alzheimer Disease and Associated Disorders"},{"issue":"13\u201314","key":"pone.0286349.ref004","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1089\/neu.2022.0012","article-title":"Glucocorticoid receptor overexpression in the dorsal hippocampus attenuates spatial learning and synaptic plasticity deficits after pediatric traumatic brain injury","volume":"39","author":"D Lengel","year":"2022","journal-title":"Journal of 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scoring function, efficient optimization, and multithreading","volume":"31","author":"O Trott","year":"2010","journal-title":"Journal of Computational Chemistry"},{"issue":"1","key":"pone.0286349.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A Daina","year":"2017","journal-title":"Scientific Reports"},{"issue":"5068.10","key":"pone.0286349.ref035","first-page":"1","article-title":"From proteins to perturbed hamiltonians: A suite of tutorials for the GROMACS-2018 molecular simulation package [article v1. 0]","volume":"1","author":"JA Lemkul","year":"2019","journal-title":"Living Journal of Computational Molecular Science"},{"issue":"4","key":"pone.0286349.ref036","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","article-title":"CHARMM general force field: A force field for drug\u2010like molecules compatible with the CHARMM all\u2010atom additive biological force fields","volume":"31","author":"K Vanommeslaeghe","year":"2010","journal-title":"Journal of Computational Chemistry"},{"issue":"4","key":"pone.0286349.ref037","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.phymed.2007.02.002","article-title":"Acetylcholinesterase inhibitors from plants","volume":"14","author":"PK Mukherjee","year":"2007","journal-title":"Phytomedicine"},{"issue":"7","key":"pone.0286349.ref038","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"H Hampel","year":"2018","journal-title":"Brain"},{"issue":"2","key":"pone.0286349.ref039","first-page":"1","article-title":"The Down syndrome-associated protein, regulator of calcineurin-1, is altered in Alzheimer\u2019s disease and dementia with Lewy bodies","volume":"9","author":"N Malakooti","year":"2019","journal-title":"Journal of Alzheimer\u2019s disease & Parkinsonism"},{"key":"pone.0286349.ref040","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/B978-0-444-64183-0.00008-7","article-title":"Alkaloids as potential multi-target drugs to treat Alzheimer\u2019s disease","volume":"61","author":"JA Lima","year":"2019","journal-title":"Studies in Natural Products Chemistry"},{"issue":"2","key":"pone.0286349.ref041","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/13543776.2021.1974001","article-title":"A patent review of berberine and its derivatives with various pharmacological activities (2016\u20132020)","volume":"32","author":"Y Kong","year":"2022","journal-title":"Expert Opinion on Therapeutic Patents"},{"issue":"2","key":"pone.0286349.ref042","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4196\/kjpp.2012.16.2.79","article-title":"Phellodendron amurense and its major alkaloid 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DC","volume":"2","author":"HR Naika","year":"2008","journal-title":"Research Journal of Medicinal Plants"},{"key":"pone.0286349.ref046","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/s11418-010-0490-x","article-title":"Application of 1 H-NMR spectroscopy to validation of berberine alkaloid reagents and to chemical evaluation of Coptidis Rhizoma","volume":"65","author":"K Hasada","year":"2011","journal-title":"Journal of Natural Medicines"},{"issue":"1\u20133","key":"pone.0286349.ref047","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejphar.2010.07.037","article-title":"Berberine induces apoptosis in breast cancer cells (MCF-7) through mitochondrial-dependent pathway","volume":"645","author":"JB Patil","year":"2010","journal-title":"European Journal of Pharmacology"},{"key":"pone.0286349.ref048","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neurobiolaging.2018.10.026","article-title":"Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APPNL-GF\/NL-GF) model of Alzheimer\u2019s disease","volume":"75","author":"J Mehla","year":"2019","journal-title":"Neurobiology of Aging"},{"issue":"1","key":"pone.0286349.ref049","first-page":"53","article-title":"Neuroprotective effect of berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia","volume":"21","author":"ML Aski","year":"2018","journal-title":"Iranian Journal of Basic Medical Sciences"},{"issue":"8","key":"pone.0286349.ref050","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1248\/bpb.32.1433","article-title":"Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids","volume":"32","author":"HA Jung","year":"2009","journal-title":"Biological and Pharmaceutical Bulletin"},{"key":"pone.0286349.ref051","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.fct.2017.11.025","article-title":"Neuroprotective effect of berberine against 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